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Immunodeficiency 83, susceptibility to viral infections(IIAE2; IMD83)

MedGen UID:
416638
Concept ID:
C2751803
Disease or Syndrome
Synonym: Herpes simplex encephalitis 2
 
Gene (location): TLR3 (4q35.1)
 
Monarch Initiative: MONDO:0800187
OMIM®: 613002

Definition

Immunodeficiency-83 (IMD83) is characterized by increased susceptibility to severe viral infections, including herpes simplex virus (HSV), varicella zoster virus (VZV), influenza A virus (IAV), hantavirus, and possibly respiratory syncytial virus (RSV). The age at onset varies widely from infancy to adulthood, and there is incomplete penetrance. The susceptibility to encephalitis or pneumonitis appears to result from impaired TLR3-dependent interferon production by nonhematopoietic cells that reside within the central nervous system (CNS) or lung epithelial cells (review by Zhang et al., 2013; summary by Mork et al., 2015; Sironi et al., 2017, Lim et al., 2019, Partanen et al., 2020). For a general phenotypic description of herpes simplex encephalitis (HSE) and a discussion of genetic heterogeneity of acute infection-induced encephalopathy, see 610551. [from OMIM]

Clinical features

From HPO
Confusion
MedGen UID:
3587
Concept ID:
C0009676
Mental or Behavioral Dysfunction
Lack of clarity and coherence of thought, perception, understanding, or action.
Gliosis
MedGen UID:
4899
Concept ID:
C0017639
Pathologic Function
Gliosis is the focal proliferation of glial cells in the central nervous system.
Hemiparesis
MedGen UID:
6783
Concept ID:
C0018989
Finding
Loss of strength in the arm, leg, and sometimes face on one side of the body. Hemiplegia refers to a complete loss of strength, whereas hemiparesis refers to an incomplete loss of strength.
Lethargy
MedGen UID:
7310
Concept ID:
C0023380
Sign or Symptom
A state of fatigue, either physical or mental slowness and sluggishness, with difficulties in initiating or performing simple tasks. Distinguished from apathy which implies indifference and a lack of desire or interest in the task. A person with lethargy may have the desire, but not the energy to engage in personal or socially relevant tasks.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
EEG abnormality
MedGen UID:
56235
Concept ID:
C0151611
Finding
Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp.
Mental deterioration
MedGen UID:
66713
Concept ID:
C0234985
Mental or Behavioral Dysfunction
Loss of previously present mental abilities, generally in adults.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Meningitis
MedGen UID:
6298
Concept ID:
C0025289
Disease or Syndrome
Inflammation of the meninges.
Herpes simplex encephalitis
MedGen UID:
75794
Concept ID:
C0276226
Disease or Syndrome
Infection of the brain parenchyma with herpes simplex virus, resulting in inflammation of the brain parenchyma with neurologic dysfunction.

Professional guidelines

PubMed

Bwire GM, Aiko BG, Mosha IH, Kilapilo MS, Mangara A, Kazonda P, Swai JP, Swalehe O, Jordan MR, Vercauteren J, Sando D, Temba D, Shao A, Mauka W, Decouttere C, Vandaele N, Sangeda RZ, Killewo J, Vandamme AM
Sci Rep 2023 Nov 22;13(1):20493. doi: 10.1038/s41598-023-47795-1. PMID: 37993493Free PMC Article
González-Duran JA, Plaza RV, Luna L, Arbeláez MP, Deviaene M, Keynan Y, Rueda ZV, Marin D
Colomb Med (Cali) 2021 Oct-Dec;52(4):e2024875. Epub 2021 Dec 8 doi: 10.25100/cm.v52i3.4875. PMID: 35571589Free PMC Article
Alsulami K, Bolastig N, Dupuy FP, Mabanga T, Gilbert L, Kiani Z, Routy JP, Bruneau J, Thomas R, Tremblay C, Tsoukas CM, Szabo J, Côté P, Trottier B, LeBlanc R, Rouleau D, Bernard NF; investigators in the Montreal Primary HIV Infection cohort
J Virol 2021 Jul 26;95(16):e0041721. doi: 10.1128/JVI.00417-21. PMID: 34076484Free PMC Article

Recent clinical studies

Etiology

Fu L, Tian T, Wang B, Lu Z, Bian J, Zhang W, Wu X, Li X, Siow RC, Fang EF, He N, Zou H
Lancet Healthy Longev 2024 Jan;5(1):e17-e30. doi: 10.1016/S2666-7568(23)00214-3. PMID: 38183996
Kay AW, Ness T, Verkuijl SE, Viney K, Brands A, Masini T, González Fernández L, Eisenhut M, Detjen AK, Mandalakas AM, Steingart KR, Takwoingi Y
Cochrane Database Syst Rev 2022 Sep 6;9(9):CD013359. doi: 10.1002/14651858.CD013359.pub3. PMID: 36065889Free PMC Article
Segal-Maurer S, DeJesus E, Stellbrink HJ, Castagna A, Richmond GJ, Sinclair GI, Siripassorn K, Ruane PJ, Berhe M, Wang H, Margot NA, Dvory-Sobol H, Hyland RH, Brainard DM, Rhee MS, Baeten JM, Molina JM; CAPELLA Study Investigators
N Engl J Med 2022 May 12;386(19):1793-1803. doi: 10.1056/NEJMoa2115542. PMID: 35544387
Toubiana J, Okada S, Hiller J, Oleastro M, Lagos Gomez M, Aldave Becerra JC, Ouachée-Chardin M, Fouyssac F, Girisha KM, Etzioni A, Van Montfrans J, Camcioglu Y, Kerns LA, Belohradsky B, Blanche S, Bousfiha A, Rodriguez-Gallego C, Meyts I, Kisand K, Reichenbach J, Renner ED, Rosenzweig S, Grimbacher B, van de Veerdonk FL, Traidl-Hoffmann C, Picard C, Marodi L, Morio T, Kobayashi M, Lilic D, Milner JD, Holland S, Casanova JL, Puel A; International STAT1 Gain-of-Function Study Group
Blood 2016 Jun 23;127(25):3154-64. Epub 2016 Apr 25 doi: 10.1182/blood-2015-11-679902. PMID: 27114460Free PMC Article
Bruchfeld J, Correia-Neves M, Källenius G
Cold Spring Harb Perspect Med 2015 Feb 26;5(7):a017871. doi: 10.1101/cshperspect.a017871. PMID: 25722472Free PMC Article

Diagnosis

Kay AW, Ness T, Verkuijl SE, Viney K, Brands A, Masini T, González Fernández L, Eisenhut M, Detjen AK, Mandalakas AM, Steingart KR, Takwoingi Y
Cochrane Database Syst Rev 2022 Sep 6;9(9):CD013359. doi: 10.1002/14651858.CD013359.pub3. PMID: 36065889Free PMC Article
Abate G, Stapleton JT, Rouphael N, Creech B, Stout JE, El Sahly HM, Jackson L, Leyva FJ, Tomashek KM, Tibbals M, Watson N, Miller A, Charbek E, Siegner J, Sokol-Anderson M, Nayak R, Dahlberg G, Winokur P, Alaaeddine G, Beydoun N, Sokolow K, Kown NP, Phillips S, Baker AW, Turner N, Walter E, Guy E, Frey S
Clin Infect Dis 2021 Apr 8;72(7):1127-1137. doi: 10.1093/cid/ciaa252. PMID: 32198521Free PMC Article
Moradi L, Cheraghi T, Yazdani R, Azizi G, Rasouli S, Zavareh FT, Parvaneh L, Parvaneh N, Sohani M, Delavari S, Abolhassani H, Rezaei N, Aghamohammadi A
Allergol Immunopathol (Madr) 2019 Sep-Oct;47(5):491-498. Epub 2019 Jul 23 doi: 10.1016/j.aller.2019.02.004. PMID: 31350062
Soti S, Corey KE, Lake JE, Erlandson KM
Curr HIV/AIDS Rep 2018 Jun;15(3):212-222. doi: 10.1007/s11904-018-0392-1. PMID: 29671204Free PMC Article
Hickey AJ, Gounder L, Moosa MY, Drain PK
BMC Infect Dis 2015 May 6;15:209. doi: 10.1186/s12879-015-0944-6. PMID: 25943103Free PMC Article

Therapy

Kay AW, Ness T, Verkuijl SE, Viney K, Brands A, Masini T, González Fernández L, Eisenhut M, Detjen AK, Mandalakas AM, Steingart KR, Takwoingi Y
Cochrane Database Syst Rev 2022 Sep 6;9(9):CD013359. doi: 10.1002/14651858.CD013359.pub3. PMID: 36065889Free PMC Article
Segal-Maurer S, DeJesus E, Stellbrink HJ, Castagna A, Richmond GJ, Sinclair GI, Siripassorn K, Ruane PJ, Berhe M, Wang H, Margot NA, Dvory-Sobol H, Hyland RH, Brainard DM, Rhee MS, Baeten JM, Molina JM; CAPELLA Study Investigators
N Engl J Med 2022 May 12;386(19):1793-1803. doi: 10.1056/NEJMoa2115542. PMID: 35544387
Emu B, Fessel J, Schrader S, Kumar P, Richmond G, Win S, Weinheimer S, Marsolais C, Lewis S
N Engl J Med 2018 Aug 16;379(7):645-654. doi: 10.1056/NEJMoa1711460. PMID: 30110589
Bruchfeld J, Correia-Neves M, Källenius G
Cold Spring Harb Perspect Med 2015 Feb 26;5(7):a017871. doi: 10.1101/cshperspect.a017871. PMID: 25722472Free PMC Article
Hilber AM, Francis SC, Chersich M, Scott P, Redmond S, Bender N, Miotti P, Temmerman M, Low N
PLoS One 2010 Feb 9;5(2):e9119. doi: 10.1371/journal.pone.0009119. PMID: 20161749Free PMC Article

Prognosis

Chaix ML, Terracol L, Nere ML, Stefic K, Lascoux-Combe C, Manda V, Sellier P, Maylin S, Molina JM, Liegeon G, Delaugerre C, Salmona M
J Med Virol 2024 Oct;96(10):e29948. doi: 10.1002/jmv.29948. PMID: 39363782
Ridolfi F, Amorim G, Peetluk LS, Haas DW, Staats C, Araújo-Pereira M, Cordeiro-Santos M, Kritski AL, Figueiredo MC, Andrade BB, Rolla VC, Sterling TR; Regional Prospective Observational Research in Tuberculosis (RePORT)–Brazil Consortium
J Infect Dis 2024 Mar 14;229(3):813-823. doi: 10.1093/infdis/jiae025. PMID: 38262629Free PMC Article
Alsulami K, Bolastig N, Dupuy FP, Mabanga T, Gilbert L, Kiani Z, Routy JP, Bruneau J, Thomas R, Tremblay C, Tsoukas CM, Szabo J, Côté P, Trottier B, LeBlanc R, Rouleau D, Bernard NF; investigators in the Montreal Primary HIV Infection cohort
J Virol 2021 Jul 26;95(16):e0041721. doi: 10.1128/JVI.00417-21. PMID: 34076484Free PMC Article
Soti S, Corey KE, Lake JE, Erlandson KM
Curr HIV/AIDS Rep 2018 Jun;15(3):212-222. doi: 10.1007/s11904-018-0392-1. PMID: 29671204Free PMC Article
Toubiana J, Okada S, Hiller J, Oleastro M, Lagos Gomez M, Aldave Becerra JC, Ouachée-Chardin M, Fouyssac F, Girisha KM, Etzioni A, Van Montfrans J, Camcioglu Y, Kerns LA, Belohradsky B, Blanche S, Bousfiha A, Rodriguez-Gallego C, Meyts I, Kisand K, Reichenbach J, Renner ED, Rosenzweig S, Grimbacher B, van de Veerdonk FL, Traidl-Hoffmann C, Picard C, Marodi L, Morio T, Kobayashi M, Lilic D, Milner JD, Holland S, Casanova JL, Puel A; International STAT1 Gain-of-Function Study Group
Blood 2016 Jun 23;127(25):3154-64. Epub 2016 Apr 25 doi: 10.1182/blood-2015-11-679902. PMID: 27114460Free PMC Article

Clinical prediction guides

Segal-Maurer S, DeJesus E, Stellbrink HJ, Castagna A, Richmond GJ, Sinclair GI, Siripassorn K, Ruane PJ, Berhe M, Wang H, Margot NA, Dvory-Sobol H, Hyland RH, Brainard DM, Rhee MS, Baeten JM, Molina JM; CAPELLA Study Investigators
N Engl J Med 2022 May 12;386(19):1793-1803. doi: 10.1056/NEJMoa2115542. PMID: 35544387
Alsulami K, Bolastig N, Dupuy FP, Mabanga T, Gilbert L, Kiani Z, Routy JP, Bruneau J, Thomas R, Tremblay C, Tsoukas CM, Szabo J, Côté P, Trottier B, LeBlanc R, Rouleau D, Bernard NF; investigators in the Montreal Primary HIV Infection cohort
J Virol 2021 Jul 26;95(16):e0041721. doi: 10.1128/JVI.00417-21. PMID: 34076484Free PMC Article
Emu B, Fessel J, Schrader S, Kumar P, Richmond G, Win S, Weinheimer S, Marsolais C, Lewis S
N Engl J Med 2018 Aug 16;379(7):645-654. doi: 10.1056/NEJMoa1711460. PMID: 30110589
Toubiana J, Okada S, Hiller J, Oleastro M, Lagos Gomez M, Aldave Becerra JC, Ouachée-Chardin M, Fouyssac F, Girisha KM, Etzioni A, Van Montfrans J, Camcioglu Y, Kerns LA, Belohradsky B, Blanche S, Bousfiha A, Rodriguez-Gallego C, Meyts I, Kisand K, Reichenbach J, Renner ED, Rosenzweig S, Grimbacher B, van de Veerdonk FL, Traidl-Hoffmann C, Picard C, Marodi L, Morio T, Kobayashi M, Lilic D, Milner JD, Holland S, Casanova JL, Puel A; International STAT1 Gain-of-Function Study Group
Blood 2016 Jun 23;127(25):3154-64. Epub 2016 Apr 25 doi: 10.1182/blood-2015-11-679902. PMID: 27114460Free PMC Article
Zhao J, Lin G, Zhang WH, Ge M, Zhang Y
Int J Tuberc Lung Dis 2013 Nov;17(11):1472-8. doi: 10.5588/ijtld.13.0264. PMID: 24125453

Recent systematic reviews

Kay AW, Ness T, Verkuijl SE, Viney K, Brands A, Masini T, González Fernández L, Eisenhut M, Detjen AK, Mandalakas AM, Steingart KR, Takwoingi Y
Cochrane Database Syst Rev 2022 Sep 6;9(9):CD013359. doi: 10.1002/14651858.CD013359.pub3. PMID: 36065889Free PMC Article
Olaru ID, Tacconelli E, Yeung S, Ferrand RA, Stabler RA, Hopkins H, Aiken AM, Kranzer K
Clin Microbiol Infect 2021 Jun;27(6):846-853. Epub 2021 Apr 1 doi: 10.1016/j.cmi.2021.03.026. PMID: 33813126
Seid MA, Ayalew MB, Muche EA, Gebreyohannes EA, Abegaz TM
BMJ Open 2018 Sep 25;8(9):e022111. doi: 10.1136/bmjopen-2018-022111. PMID: 30257846Free PMC Article
Hickey AJ, Gounder L, Moosa MY, Drain PK
BMC Infect Dis 2015 May 6;15:209. doi: 10.1186/s12879-015-0944-6. PMID: 25943103Free PMC Article
Hilber AM, Francis SC, Chersich M, Scott P, Redmond S, Bender N, Miotti P, Temmerman M, Low N
PLoS One 2010 Feb 9;5(2):e9119. doi: 10.1371/journal.pone.0009119. PMID: 20161749Free PMC Article

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